PMC:4621299 / 15430-16595
Annnotations
{"target":"http://pubannotation.org/docs/sourcedb/PMC/sourceid/4621299","sourcedb":"PMC","sourceid":"4621299","source_url":"https://www.ncbi.nlm.nih.gov/pmc/4621299","text":"Genetic deficiency in SNAREs was shown to be associated with the progression of neurodegenerative diseases like AD and PD. PD is marked by the presence of Lewy bodies which are principally composed of aggregated α-synuclein. Under physiological conditions, α-synuclein may regulate vesicle trafficking and promote synaptic transmission by binding directly to SNAREs and stimulating SNARE complex formation (Burré et al., 2010; Thayanidhi et al., 2010). Overexpression of wild type or the PD-associated mutant of α-synuclein (A53T) leads to cytotoxicity and inhibition of ER-to-Golgi trafficking in in vitro models which can be partially suppressed by co-overexpression of SNAREs Ykt6 or Sec22. Ykt6—a protein enriched in neurons—was more protective than Sec22 and suggests a specialized role in mammals (Hasegawa et al., 2003, 2004). In vitro binding experiments also point toward the direct interaction of α-synuclein with STX5 and GS27 along with mutant α-synuclein which destabilizes the STX5-GS27-rbet1-sec22b SNARE complex (Thayanidhi et al., 2010). This line of evidence further implicates trafficking defects in bringing about neurodegenerative cytotoxicity.","tracks":[{"project":"TEST0","denotations":[{"id":"26578865-196-204-323917","span":{"begin":421,"end":425},"obj":"[\"20798282\"]"},{"id":"26578865-221-229-323918","span":{"begin":446,"end":450},"obj":"[\"20392839\"]"},{"id":"26578865-127-135-323919","span":{"begin":821,"end":825},"obj":"[\"12589064\"]"},{"id":"26578865-133-141-323920","span":{"begin":827,"end":831},"obj":"[\"15331663\"]"},{"id":"26578865-214-222-323921","span":{"begin":1048,"end":1052},"obj":"[\"20392839\"]"}],"attributes":[{"subj":"26578865-196-204-323917","pred":"source","obj":"TEST0"},{"subj":"26578865-221-229-323918","pred":"source","obj":"TEST0"},{"subj":"26578865-127-135-323919","pred":"source","obj":"TEST0"},{"subj":"26578865-133-141-323920","pred":"source","obj":"TEST0"},{"subj":"26578865-214-222-323921","pred":"source","obj":"TEST0"}]},{"project":"0_colil","denotations":[{"id":"26578865-20798282-323917","span":{"begin":421,"end":425},"obj":"20798282"},{"id":"26578865-20392839-323918","span":{"begin":446,"end":450},"obj":"20392839"},{"id":"26578865-12589064-323919","span":{"begin":821,"end":825},"obj":"12589064"},{"id":"26578865-15331663-323920","span":{"begin":827,"end":831},"obj":"15331663"},{"id":"26578865-20392839-323921","span":{"begin":1048,"end":1052},"obj":"20392839"}],"attributes":[{"subj":"26578865-20798282-323917","pred":"source","obj":"0_colil"},{"subj":"26578865-20392839-323918","pred":"source","obj":"0_colil"},{"subj":"26578865-12589064-323919","pred":"source","obj":"0_colil"},{"subj":"26578865-15331663-323920","pred":"source","obj":"0_colil"},{"subj":"26578865-20392839-323921","pred":"source","obj":"0_colil"}]},{"project":"2_test","denotations":[{"id":"26578865-20798282-38257398","span":{"begin":421,"end":425},"obj":"20798282"},{"id":"26578865-20392839-38257399","span":{"begin":446,"end":450},"obj":"20392839"},{"id":"26578865-12589064-38257400","span":{"begin":821,"end":825},"obj":"12589064"},{"id":"26578865-15331663-38257401","span":{"begin":827,"end":831},"obj":"15331663"},{"id":"26578865-20392839-38257402","span":{"begin":1048,"end":1052},"obj":"20392839"}],"attributes":[{"subj":"26578865-20798282-38257398","pred":"source","obj":"2_test"},{"subj":"26578865-20392839-38257399","pred":"source","obj":"2_test"},{"subj":"26578865-12589064-38257400","pred":"source","obj":"2_test"},{"subj":"26578865-15331663-38257401","pred":"source","obj":"2_test"},{"subj":"26578865-20392839-38257402","pred":"source","obj":"2_test"}]}],"config":{"attribute types":[{"pred":"source","value type":"selection","values":[{"id":"TEST0","color":"#93d8ec","default":true},{"id":"0_colil","color":"#ece693"},{"id":"2_test","color":"#cc93ec"}]}]}}